Abstract

Background

IL28B and ITPA genetic variants are associated with the outcome of pegylated-interferon
and ribavirin (PEG-IFN/RBV) therapy. However, the significance of these genetic variants
in cirrhotic patients following splenectomy has not been determined.

Methods

Thirty-seven patients with HCV-induced cirrhosis who underwent laparoscopic splenectomy
(Spx group) and 90 who did not (non-Spx group) were genotyped for IL28B and ITPA.
The outcome or adverse effects were compared in each group. Interferon-stimulated
gene 15 (ISG15) and protein kinase R expression in the spleen was measured using total
RNA extracted from exenterate spleen.

Results

Sustained virological response (SVR) rate was higher in patients carrying IL28B major
genotype following splenectomy (50% vs 27.3%) and in patients carrying minor genotype
in the Spx group compared to non-Spx group (27.3% vs 3.6%, P < 0.05). Pretreatment splenic ISG expression was higher in patients carrying IL28B
major. There was no difference in progression of anemia or thrombocytopenia between
patients carrying each ITPA genotype in the Spx group. Although splenectomy did not
increase hemoglobin (Hb) level, Hb decline tended to be greater in the non-Spx group.
In contrast, splenectomy significantly increased platelet count (61.1 × 103/μl vs 168.7 × 103/μl, P < 0.01), which was maintained during the course of PEG-IFN/RBV therapy.

Conclusions

IL28B genetic variants correlated with response to PEG-IFN/RBV following splenectomy.
Splenectomy improved SVR rate among patients carrying IL28B minor genotype and protected
against anemia and thrombocytopenia during the course of PEG-IFN/RBV therapy regardless
of ITPA genotype.